Multicenter phase II trial of temsirolimus and bevacizumab in pancreatic neuroendocrine tumors

Timothy J. Hobday, Rui Qin, Diane Reidy-Lagunes, Malcolm J. Moore, Jonathan Strosberg, Andreas Kaubisch, Manisha Shah, Hedy Lee Kindler, Heinz Josef Lenz, Helen Chen, Charles Erlichman

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63 Scopus citations

Abstract

Purpose: There are few effective therapies for pancreatic neuroendocrine tumors (PNETs). Recent placebo-controlled phase III trials of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the vascular endothelial growth factor (VEGF)/platelet-derived growth factor receptor inhibitor sunitinib have noted improved progression-free survival (PFS). Preclinical studies have suggested enhanced antitumor effects with combined mTOR and VEGF pathway-targeted therapy. We conducted a clinical trial to evaluate combination therapy against these targets in PNETs. Patients and Methods: We conducted a two-stage single-arm phase II trial of the mTOR inhibitor temsirolimus 25 mg intravenously (IV) once per week and the VEGF-A monoclonal antibody bevacizumab 10 mg/kg IV once every 2 weeks in patients with well or moderately differentiated PNETs and progressive disease by RECIST within 7 months of study entry. Coprimary end points were tumor response rate and 6-month PFS. Results: A total of 58 patients were enrolled, and 56 patients were eligible for response assessment. Confirmed response rate (RR) was 41% (23 of 56 patients). PFS at 6 months was 79% (44 of 56). Median PFS was 13.2 months (95% CI, 11.2 to 16.6). Median overall survival was 34 months (95% CI, 27.1 to not reached). For evaluable patients, the most common grade 3 to 4 adverse events attributed to therapy were hypertension (21%), fatigue (16%), lymphopenia (14%), and hyperglycemia (14%). Conclusion: The combination of temsirolimus and bevacizumab had substantial activity and reasonable tolerability in a multicenter phase II trial, with RR of 41%, well in excess of single targeted agents in patients with progressive PNETs. Six-month PFS was a notable 79% in a population of patients with disease progression by RECIST criteria within 7 months of study entry. On the basis of this trial, continued evaluation of combination mTOR and VEGF pathway inhibitors is warranted.

Original languageEnglish (US)
Pages (from-to)1551-1556
Number of pages6
JournalJournal of Clinical Oncology
Volume33
Issue number14
DOIs
StatePublished - May 10 2015

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hobday, T. J., Qin, R., Reidy-Lagunes, D., Moore, M. J., Strosberg, J., Kaubisch, A., Shah, M., Kindler, H. L., Lenz, H. J., Chen, H., & Erlichman, C. (2015). Multicenter phase II trial of temsirolimus and bevacizumab in pancreatic neuroendocrine tumors. Journal of Clinical Oncology, 33(14), 1551-1556. https://doi.org/10.1200/JCO.2014.56.2082